Nuclear receptors belong to a highly conserved superfamily of transducers which play a key role in processing of extracellular signals into gene expression responses during development, differentiation, reproduction and integrated homeostasis of all vertebrates and many invertebrates. These receptors act as transcriptional regulators and respond to lipophilic ligands, such as steroid and thyroid hormones, retinoids, vitamin D, oxysterols, bile acids and certain fatty acids. The family also includes a number or orphan receptors for which biochemical functions are unknown and ligands are currently being sought. Because they regulate so many cellular functions, nuclear receptors are important and promising targets for drugs in numerous medical fields, including those of cancer, inflammation, endocrine and metabolic disorders, hypertension, and reproductive functions. The present challenges are first to elucidate how the structural organization of the diverse multiprotein-receptor complexes is related to the molecular mechanisms underlying transcriptional activation and repression of target genes, and second to integrate, at the organism level, the physiological processes and signal transduction pathways regulated through nuclear receptors with those controlled through cell membrane receptors. This meeting will bring together leading experts, as well as younger investigators and trainees in a manner that integrates the diverse aspects of nuclear receptor biology, encompassing three dimensional structure of multiprotein-receptor complexes, molecular mechanisms of action of nuclear receptors and their coregulators at their target genes, genetic dissection of receptor-mediated physiological functions during development and postnatal life through conditional somatic mutagenesis, identification of ligands and physiological roles for orphan receptors, ligand design, use of functional genomics to characterize receptor-regulated gene networks, and development of new technologies to aid in drug discovery.